当前位置: X-MOL 学术J. Biol. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma
Journal of Biological Chemistry ( IF 5.5 ) Pub Date : 2023-05-29 , DOI: 10.1016/j.jbc.2023.104873
Wei-Hong Zheng 1 , Zhi-Qing Long 2 , Zi-Qi Zheng 2 , Lu-Lu Zhang 3 , Ye-Lin Liang 2 , Zhi-Xuan Li 2 , Jia-Wei Lv 4 , Jia Kou 4 , Xiao-Hong Hong 2 , Shi-Wei He 2 , Rui Xu 2 , Guan-Qun Zhou 4 , Na Liu 2 , Jun Ma 1 , Ying Sun 1 , Li Lin 4 , Denghui Wei 2
Affiliation  

Dysregulation of long noncoding RNAs (lncRNAs) contributes to tumorigenesis by modulating specific cancer-related pathways, but the roles of N6-methyladenosine (m6A)-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profiles in 18 pairs of NPC and normal tissues as well as in ten paired samples from NPC with or without post-treatment metastases. We discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis both in vitro and in vivo. Mechanistically, by using RNA pull-down assay combined with mass spectrometry, we found that LINC00839 interacted directly with the transcription factor, TATA-box binding protein associated factor (TAF15). Besides, chromatin immunoprecipitation and dual-luciferase report assays demonstrated that LINC00839 coordinated the recruitment of TAF15 to the promoter region of amine oxidase copper-containing 1 (AOC1), which encodes a secreted glycoprotein playing vital roles in various cancers, thereby activating AOC1 transcription in trans. In this study, potential effects of AOC1 in NPC progression were first proposed. Moreover, ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, we showed that silencing vir-like m6A methyltransferase-associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) attenuated the expression level and RNA stability of LINC00839 in an m6A-dependent manner. Taken together, our study unveils a novel oncogenic VIRMA/IGF2BP1–LINC00839–TAF15–AOC1 axis and highlights the significance and prognostic value of LINC00839 expression in NPC carcinogenesis.



中文翻译:

鼻咽癌中富含 m6A 的 lncRNA LINC00839 通过增强 TAF15 介导的胺氧化酶 AOC1 转录促进肿瘤进展

长非编码 RNA (lncRNA) 的失调通过调节特定的癌症相关途径促进肿瘤发生,但富含 N6-甲基腺苷 (m6A) 的 lncRNA 的作用和潜在机制在鼻咽癌 (NPC) 中仍然难以捉摸。在这里,我们重新分析了之前对 18 对 NPC 和正常组织以及 10 对来自有或没有治疗后转移的 NPC 样本的 lncRNA 图谱的全基因组分析。我们发现,富含致癌 m6A 的 lncRNA LINC00839在体外体内均促进了 NPC 的生长和转移,该基因在 NPC 中显着上调并与不良临床预后相关。从机制上讲,通过使用 RNA Pull-down 测定结合质谱法,我们发现LINC00839与转录因子 TATA-box 结合蛋白相关因子 (TAF15) 直接相互作用。此外,染色质免疫沉淀和双荧光素酶报告分析表明,LINC00839协调将TAF15募集到胺氧化酶含铜1( AOC1 )的启动子区域,该区域编码一种在多种癌症中发挥重要作用的分泌糖蛋白,从而激活AOC1转录。反式。在这项研究中,首次提出了AOC1在 NPC 进展中的潜在影响。此外, AOC1的异位表达部分挽救了鼻咽癌中LINC00839下调的抑制作用。此外,我们发现沉默 vir 样 m6A 甲基转移酶相关 ( VIRMA ) 和胰岛素样生长因子 2 mRNA 结合蛋白 1 ( IGF2BP1 ) 会以 m6A 依赖性方式减弱LINC00839的表达水平和 RNA 稳定性。综上所述,我们的研究揭示了一种新的致癌VIRMA/IGF2BP1- LINC00839 -TAF15-AOC1轴,并强调了LINC00839表达在鼻咽癌癌变中的意义和预后价值。

更新日期:2023-05-29
down
wechat
bug